Insular amyloidosis is associated with diabetes mellitus in aging Macaca nigra, as it is in several million aging human beings. Amyloid appears in the islets of Langerhans, and there are simultaneous changes in secretory cell structure and function. As the islet lesion develops, circulating insulin and glucagon concentrations change. The islet lesion and circulating hormone changes precede clinical appearance of impaired glucose tolerance. Normal and diabetic Macaca nigra are used to examine relationships between the islet amyloid appearance and subsequent metabolic, hormonal, and clinical changes. Concentrations of different immunoreactive forms of glucagon are examined, insulin secretory patterns are assessed, and relationships to metabolic and clinical deterioration of the monkeys are sought. Pancreatic biopsies, which are not feasible in human beings, are performed, and the islets are examined for the amount of amyloid; additional work involves quantification of viable beta and alpha cells and establishment of their relationships to hormonal and metabolic changes. Results will provide the basis: for establishment of the causes of insular amyloidosis in monkeys; for future identification of markers useful in predicting impending insular amyloidosis and diabetes in aging monkeys; and for laying groundwork for prospective studies on this syndrome in aging human beings.